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Hormonal contraception for suppression of menstruation

Hormonal contraception for suppression of menstruation
Literature review current through: Sep 2023.
This topic last updated: Aug 25, 2022.

INTRODUCTION — Several available hormonal contraceptives can be used to reduce or eliminate monthly uterine bleeding. The safety and efficacy of these methods make them desirable for patients who have medical indications for suppression of menstruation, those for whom menstrual hygiene is challenging, and those who want the convenience of not having a monthly period.

Use of hormonal contraceptives for suppression of menstruation is reviewed here. Evaluation and management of patients with abnormal uterine bleeding, as well as general principles of contraceptive selection, are discussed separately.

(See "Abnormal uterine bleeding in nonpregnant reproductive-age patients: Terminology, evaluation, and approach to diagnosis".)

(See "Abnormal uterine bleeding in nonpregnant reproductive-age patients: Management".)

(See "Contraception: Counseling and selection".)

In this topic, when discussing study results, we will use the terms "women" or "patients" as they are used in the studies presented. However, we encourage the reader to consider the specific counseling and treatment needs of transgender and gender-expansive individuals.

DEFINITION — Menstrual suppression involves the use of hormonal contraception to decrease the frequency and volume of normal menses or to suppress menses altogether (ie, achieve amenorrhea) [1,2]. Contraceptive options include combined estrogen-progestin oral pills, patches, or rings; progestin pills, injection, or implant; and levonorgestrel-releasing intrauterine devices (IUDs). In contrast to surgical procedures, such as endometrial ablation and hysterectomy, medical therapy does not irreversibly impair fertility. Menstrual suppression can be used to address medical conditions or for patient preferences regarding menses.

SAFETY OF MENSTRUAL SUPPRESSION — Menstruation (ovulation followed by withdrawal bleeding) is not physiologically necessary for patients not wishing to conceive. In fact, most modern females experience many more menstrual cycles in their lifetimes than those in prior generations because of earlier menarche, fewer pregnancies, reduced duration of breastfeeding, and later menopause [3]. Moreover, this frequent, regular ovulation may actually increase a person's risk of some diseases, such as endometriosis and ovarian cancer. Studies worldwide have consistently reported that, among individuals informed that monthly bleeding is not necessary for their health, most favor bleeding frequency less often than monthly (table 1) [4-6].

The concept that monthly bleeding is healthy has been perpetuated by oral contraceptives (OCs) that were initially designed to mimic the average length of a normal menstrual cycle. This artificial "period" had no medical benefits, and the initial choice of 21/7 (monthly) OC formulations that result in withdrawal bleeding every four weeks was arbitrary.

Continuous or long-term use of estrogen-progestin (combination) or progestin-only contraception is associated with the same medical risks as cyclic use of these medications [7]. In contrast with patients on cyclic regimens, those using continuous-dose regimens benefit from reduction of menstrual symptoms (eg, headache, genital irritation, tiredness, bloating, and pain) [8]. We educate our patients that unscheduled bleeding is common during use of extended regimens.

COMMON INDICATIONS — Suppression of menstruation can be beneficial for patients with an array of medical conditions and social needs (table 2). The beneficial mechanisms include a reduction in the volume and frequency of uterine bleeding and/or a reduction in cyclic hormonal fluctuations.

Gynecologic — Menstrual suppression can be helpful for a variety of gynecologic disorders (table 2). We discuss the option of menstrual suppression with patients in the following situations, among others:

Relief of dysmenorrhea – Dysmenorrhea refers to the recurrent, crampy, lower abdominal pain that occurs during menses. Dysmenorrhea may occur in the absence of disease (primary) or in response to another process, such as endometriosis (secondary). Menstrual suppression can relieve both.

(See "Dysmenorrhea in adult females: Clinical features and diagnosis".)

(See "Dysmenorrhea in adult females: Treatment".)

Management of symptoms related to premenstrual hormone change or mood disorders – Examples include patients with breast pain, nausea, and gastrointestinal symptoms, as well as mood changes and premenstrual dysphoric disorder.

(See "Clinical manifestations and diagnosis of premenstrual syndrome and premenstrual dysphoric disorder".)

(See "Treatment of premenstrual syndrome and premenstrual dysphoric disorder".)

Abnormal uterine bleeding – Whether related to volume (eg, heavy menstrual bleeding) or frequency (eg, ovulatory disorders), menstrual suppression can reduce or eliminate abnormal uterine bleeding.

(See "Abnormal uterine bleeding in nonpregnant reproductive-age patients: Terminology, evaluation, and approach to diagnosis".)

(See "Abnormal uterine bleeding in nonpregnant reproductive-age patients: Management".)

Prevention and treatment of excessive bleeding related to uterine leiomyoma or adenomyosis – Some patients with heavy menstrual bleeding associated with leiomyomas respond to contraception that suppresses menstruation.

(See "Uterine fibroids (leiomyomas): Treatment overview".)

Treatment of pain related to endometriosis – For patients whose endometriosis-related pain improves with hormonal contraception, continuous dosing regimens have been associated with more effective pain reduction. (See "Endometriosis: Treatment of pelvic pain", section on 'Estrogen-progestin contraceptives'.)

Reduction in risk of ovarian and endometrial cancers – While suppression of cyclic uterine bleeding does not directly impact the risk of ovarian and endometrial cancers, continuous use of combined hormonal contraceptives has been associated with reductions in these malignancies because of their role in preventing ovulation and endometrial development. (See "Combined estrogen-progestin contraception: Side effects and health concerns", section on 'Effects on cancer development'.)

Bleeding disorders — Patients with bleeding disorders or chronic anemia, either hereditary or acquired (table 2), may benefit from menstrual suppression.

Examples include the following:

Thrombocytopenia (eg, due to immune thrombocytopenia [ITP] or a primary platelet disorder)

von Willebrand disease (VWD)

Mild hemophilia or other clotting factor deficiency

Additional aspects of therapy are discussed in separate topic reviews. (See "von Willebrand disease (VWD): Treatment of major bleeding and major surgery" and "Treatment of bleeding and perioperative management in hemophilia A and B" and "Inherited platelet function disorders (IPFDs)".)

Some patients treated with an anticoagulant or those with a period of thrombocytopenia related to cancer treatment or hematopoietic cell transplantation (HCT) may also benefit from menstrual suppression for a period of time.

Some patients with iron deficiency or anemia due to another condition may be less able to tolerate blood loss. Examples include hereditary hemorrhagic telangiectasia (HHT) or certain hemoglobinopathies (sickle cell disease, transfusion-dependent thalassemia). (See "Hereditary hemorrhagic telangiectasia (HHT): Evaluation and therapy for specific vascular lesions".)

General medical — Menstrual suppression can be helpful for individuals with a variety of medical conditions (table 2). Menstrual suppression is particularly helpful for patients with severe anemia (hereditary or acquired) and conditions that are worsened by menses (eg, menstrual migraine).

Special populations — Suppression of menses can be particularly beneficial for individuals with the following issues:

Adolescents – Young teens may benefit from reducing menstrual frequency. A reduction in menstrual frequency decreases dysmenorrhea and the inconvenience of menstruation during the school day when their access to pain relievers, sanitary pads or tampons, and a change of clothes may be limited [9]. Estrogen- and progestin-containing methods are options for patients who have experienced menarche [2]. (See "Primary dysmenorrhea in adolescents".)

Patients with a cognitive and/or physical disability that makes hygienic practice challenging – These patients may find menstrual bleeding emotionally upsetting or have difficulties with the use of menstrual hygiene products, such as patients with cerebral palsy or arthritis [1,2,10].

Patients in whom avoiding menses is beneficial to their jobs or activities – These situations apply to patients who are deployed for military duties or space flight, highly competitive athletes, or pursuing extended travel [11-14]. Avoidance of uterine bleeding and menstrual symptoms may also be particularly desirable during vacations, business travel, camping/wilderness experiences, special events, and academic examinations.

Gender-expansive patients – Patients may elect menstrual suppression to reduce gender dysphoria associated with menses [2]. While doses of testosterone used by transmasculine individuals may result in amenorrhea, this does not provide contraception. Patients capable of pregnancy are counseled about options for avoiding pregnancy, if applicable.

Cost savings — A cost analysis comparing direct and indirect costs of monthly oral contraceptive cycles with an extended (trimonthly) cycle regimen reported lower annual costs with the latter [15]. Costs considered included those associated with oral contraceptive pills, hygienic products, pregnancy tests, analgesics, iron replacement therapy, visits to a clinician, and opportunity costs from missing time at work.

OUR APPROACH — Our approach is driven by the patient's baseline symptoms or medical indications for menstrual suppression, time available for onset of action, preference for reduction of menses versus amenorrhea, need for contraception, preferences for the route of administration, and potential side effects (algorithm 1). The choice of method strongly depends upon patient preferences, in addition to medical history and the side effect profiles of the options. (See "Contraception: Counseling and selection".)

We ask the following questions to help determine which choices may be most beneficial for any given patient and then follow the algorithm (algorithm 1).

Is the patient a candidate for estrogen-containing products? (See "Combined estrogen-progestin oral contraceptives: Patient selection, counseling, and use", section on 'Candidates'.)

Does the patient medically require amenorrhea? For patients who do not, do they prefer amenorrhea or cyclic bleeding of a reduced volume?

For patients who benefit from or prefer amenorrhea, how important is it to achieve complete amenorrhea?

We then counsel the patient about the available option(s) that are most likely to meet her goals.

TO ACHIEVE AMENORRHEA

Combined estrogen-progestin methods — Extended and continuous regimens of the oral pill and vaginal ring are safe and have few side effects [8]. We avoid continuous use of the transdermal contraceptive patch, releasing ethinyl estradiol and the progestin norelgestromin, because the overall ethinyl estradiol concentration is 60 percent higher in patch users compared with pill users. Concerns have been raised about possible increased risk of venous thromboembolism with extended use of this patch; however, supporting data are lacking [16,17]. An alternate transdermal contraceptive releases ethinyl estradiol and the progestin levonorgestrel. Because serum levels of ethinyl estradiol are substantially lower with this newer patch, it may be preferable if extended or continuous transdermal contraception is being considered [18]. (See "Contraception: Transdermal contraceptive patches", section on 'Risk of venous thrombotic events'.)

Extended use – Patients using extended-use regimens take active hormone pills continuously for 28 days or more followed by periodic hormone-free intervals. Extended use regimens decrease the number and frequency of withdrawal bleeds per year. Common approaches involve having the patient use the placebo oral pills, or removing the vaginal ring, at three, four, or six-month intervals to experience a withdrawal bleed. The duration of contraceptive use is determined by the individual patient's preferences; she can choose when and how often hormone-free intervals occur and time them as needed for medical treatment, work, or other obligations.

Commercial preparations of oral contraceptive pills with 91-day cycles are available (table 3). Each oral pill pack contains 84 active tablets (ethinyl estradiol and levonorgestrel [LNG]) followed by seven placebo pills. These formulations, available as generic medications, appear to provide both high contraceptive efficacy (failure rate 0.60 pregnancies per 100 women per year in a clinical trial) and endometrial safety [19,20].

Extended use of other combination pills (eg, ethinyl estradiol/drospirenone) also appears to be safe and effective [21,22].

Continuous use – Continuous use regimens have the patient use the oral pill or vaginal ring without a placebo or removal week for a continuous year. Thus, hormone-free intervals are eliminated, and the patient has no scheduled withdrawal bleeding. Data on continuous use of the vaginal ring are limited but suggest reductions in bleeding and spotting days similar to that of extended pill regimens [23-25].

Both extended use and continuous use regimens for each contraceptive method are discussed in related topics.

(See "Combined estrogen-progestin oral contraceptives: Patient selection, counseling, and use", section on 'Continuous or extended use'.)

(See "Contraception: Hormonal contraceptive vaginal rings", section on 'Insertion and use'.)

(See "Contraception: Transdermal contraceptive patches", section on 'Extended cycle use'.)

Unscheduled bleeding/spotting often occurs during the first few months of extended or continuous oral contraceptive use but then resolves. If troublesome unscheduled bleeding occurs after the first 21 days of hormone use, one approach is to stop the oral contraceptive for three days to allow withdrawal bleeding and then resume the method for at least 21 days of continuous use [21]. This approach of scheduling a short hormone-free interval can be repeated whenever bothersome breakthrough bleeding occurs, as long as the patient has taken at least 21 days of active contraceptive continuously before proceeding with a hormone-free interval. Over time, breakthrough bleeding episodes will become spaced out and stop. (See "Evaluation and management of unscheduled bleeding in individuals using hormonal contraception".)

Progestin-only methods

First tier

Depot medroxyprogesterone acetate — Depot medroxyprogesterone acetate (DMPA) inhibits ovulation and reduces or eliminates uterine bleeding. Fifty to 75 percent of patients who use DMPA for one year experience amenorrhea, which becomes more common as the duration of use increases [26]. Thus, prolonged use of this agent enhances reduction of menstruation-related symptoms. DMPA is given by intramuscular or subcutaneous (formulations differ by intended route) injection at 90-day intervals. DMPA use is discussed in detail in separate topics.

(See "Depot medroxyprogesterone acetate (DMPA): Efficacy, side effects, metabolic impact, and benefits", section on 'Menstrual changes'.)

(See "Depot medroxyprogesterone acetate (DMPA): Formulations, patient selection and drug administration".)

DMPA is a good choice for inducing amenorrhea in patients in whom estrogen-progestin contraceptives or a LNG-releasing intrauterine device (LNG 52 mg IUD) is either contraindicated, causes additional health concerns, or is not desired by the patient. Initial irregular bleeding is the most common adverse effect. Additional adverse effects, such as acne or other skin problems (related to its androgenicity), headache, and depression, resulted in discontinuation by three years in approximately 70 percent of patients in one trial [27]. Although use of DMPA reduces bone mineral density, bone loss is mostly reversed after cessation of therapy. DMPA use is discussed in detail separately. (See "Depot medroxyprogesterone acetate (DMPA): Efficacy, side effects, metabolic impact, and benefits", section on 'Reduction in bone mineral density'.)

Return of fertility upon discontinuation of contraceptive injections may be delayed compared with other methods. (See "Depot medroxyprogesterone acetate (DMPA): Formulations, patient selection and drug administration", section on 'Return to fertility after discontinuation'.)

For individuals who choose not to use intramuscular or subcutaneous injections because of concern for bleeding or infection, norethindrone acetate (NETA) becomes a first-tier treatment option. Such patients may include those with thrombocytopenia or neutropenia. (See 'Norethindrone acetate' below.)

Levonorgestrel intrauterine device (LNG 52 mg) — The LNG 52 mg IUDs are the best studied progestin-only modality for reducing the frequency and volume of menstrual blood loss. As an example, after one year of use, amenorrhea is reported by approximately 20 percent of LNG 52 mg IUD users compared with 6 percent of LNG 13.5 users [28-30]. At the end of two years of use, 30 to 50 percent of LNG 52 users reported amenorrhea compared with 12 percent of patients using the LNG 13.5 [30,31]. Therefore, patients who prefer to avoid menstrual bleeding may benefit from a 52 mg device. However, as with DMPA, the time to achieve amenorrhea may take a year or more. A detailed discussion of the LNG doses, efficacy, duration of use, and amenorrhea rates for the various LNG IUDs is presented separately.

(See "Intrauterine contraception: Background and device types", section on 'Devices and characteristics'.)

(See "Intrauterine contraception: Background and device types", section on 'Levonorgestrel-releasing IUDs'.)

LNG IUDs are a good choice for reducing uterine bleeding in patients with hemostatic disorders and patients who cannot use, or prefer to avoid, estrogen-containing methods [32]. Because ovulation-related bleeding along with heavy menses is a concern for some patients with hemostatic disorders, in selected patients, concomitant use of an LNG IUD and combination oral contraceptive or DMPA may be helpful [33]. In addition, clinicians should be aware that when a LNG 52 mg IUD is used to control heavy menstrual bleeding (HMB), including in patients with bleeding disorders, suppression of menstruation may stop prior to the six-year replacement time. When this occurs, patients may benefit from early replacement of the IUD [34]. A detailed discussion of use of the LNG IUD in patients with HMB or anovulatory bleeding can be found separately. (See "Abnormal uterine bleeding in nonpregnant reproductive-age patients: Management", section on 'Levonorgestrel intrauterine device'.)

As the lower dose LNG IUDs do not typically result in amenorrhea, we do not use them for this indication. However, they can be helpful for patients who wish to maintain cyclic withdrawal bleeding of a reduced volume. (See 'Levonorgestrel intrauterine device (LNG 19.5 mg)' below.)

Second tier

Norethindrone acetate — Oral NETA (5 mg tablets taken orally three times daily) also reduces menstrual blood [35]. In one study including 22 patients with HMB who received cyclical NETA therapy, blood loss was reduced by 87 percent in patients with idiopathic HMB [35]. However, none of these patients experienced amenorrhea during the three-month study period, and only an approximate one-quarter elected to continue with the treatment once the study ended. When compared with the LNG IUD, the two therapies produced an equivalent reduction in menstrual blood loss, but patient satisfaction was much higher with the IUD (76 versus 22 percent after three cycles).

In our experience, a lower dose of NETA (5 mg orally daily) reduces blood loss and often results in amenorrhea when taken continuously in patients suffering from HMB, including those with uterine fibroids or anovulatory uterine bleeding. We find that continuous, rather than cyclic, use of NETA is most effective in reducing or eliminating HMB and represents an easier regimen for compliance. Unfortunately, clinical trial data have not addressed continuous use of NETA in patients with HMB. However, a study assessing six months of continuous NETA 2.5 mg daily in women with endometriosis reported that 94 percent (84/89) of participants became amenorrheic [36]. Clinically, we find that the use of NETA is limited by its adverse effects including unpleasant mood symptoms, increased appetite, and bloating. Reducing the dose of NETA may reduce these side effects. In our experience, some patients who have achieved satisfactory menstrual suppression with 5 mg of NETA daily successfully transition to 2.5 mg daily (cutting the 5 mg tablets in half). However, other patients attempting to lower the dose may experience an increase in bleeding or spotting, which responds to restoring the initial higher dose of NETA. Even though it is available as a generic formulation, NETA is typically more costly than oral contraceptives or DMPA.

Of note, 5 mg or 2.5 mg of NETA represents a dose higher than that required for contraception. For example, commonly used estrogen-progestin contraceptives contain NETA 1 mg daily. The dose is also substantially higher than that of the norethindrone 0.35 mg progestin-only contraceptive pill, which is not typically used for this indication, as unscheduled bleeding is much more common than amenorrhea. (See "Contraception: Progestin-only pills (POPs)", section on 'Side effects'.)

Etonogestrel implant — The etonogestrel-progestin implant is less satisfactory for suppression of menstruation than the other methods discussed above. During the first two years of use of the single-rod etonogestrel implant (commercial name Nexplanon), 22 percent of patients developed amenorrhea, 34 percent had fewer than three bleeding/spotting episodes in 90 days, and the remainder had frequent or prolonged episodes of uterine bleeding [37]. However, the etonogestrel implant can be a good option for patients who desire a highly reliable long-acting progestin-only contraceptive and are willing to accept an approximately 50 percent likelihood of reduced bleeding. In contrast with patients using LNG 52 mg IUDs or DMPA injections, amenorrhea does not increase with ongoing duration of implant use. The implant is approved for up to three years of contraception, although studies support its efficacy through five years [38,39]. (See "Contraception: Etonogestrel implant".)

GnRH analogues

GnRH agonists – Gonadotropin-releasing hormone (GnRH) agonists include nafarelin, leuprolide, buserelin, goserelin, and triptorelin. Agonists, typically given as leuprolide, eliminate menstruation by suppressing GnRH pulsatility from the pituitary. However, use of GnRH agonists is limited for menstrual suppression in the absence of other clinical indications such as medical need for amenorrhea or endometriosis-related pain, because of the resultant menopausal side effects. However, for patients who benefit from rapid induction of amenorrhea, such as those about to receive chemotherapeutic agents or undergo bone marrow transplant, GnRH agonists will be effective in approximately one menstrual cycle. Other indications for GnRH agonists include preoperative treatment of anemic patients when surgery is planned for leiomyoma (ie, uterine fibroids).

GnRH antagonists – The oral GnRH antagonist elagolix is indicated for the treatment of pain associated with endometriosis. However, because the incidence of amenorrhea associated with this medication is <10 percent, elagolix is not recommended when the goal is achieving amenorrhea [40]. (See "Endometriosis: Treatment of pelvic pain".)

Endometriosis is a separate indication for use of GnRH analogues, and the pharmacology, side effects, and need for add-back therapy are presented in that topic review. (See "Endometriosis: Long-term treatment with gonadotropin-releasing hormone agonists".)

FOR REDUCTION OF CYCLIC WITHDRAWAL BLEEDING

Cyclic estrogen-progestin methods — Cyclic use of estrogen-progestin contraceptives (oral pills, transdermal patch, and vaginal ring) is a reasonable first-line therapy if the goal is reduction, but not necessarily elimination, of monthly blood flow and there are no contraindications to estrogen administration (eg, previous thromboembolic event or stroke, history of an estrogen-dependent tumor, ≥35 years of age and a cigarette smoker, active severe liver disease, undiagnosed abnormal uterine bleeding). (See "Combined estrogen-progestin oral contraceptives: Patient selection, counseling, and use".)

Regardless of product, cyclic dosing regimens typically involve three weeks of exposure to the combined estrogen-progestin followed by a week of no exposure (achieved with oral pill placebo tablets or removal of the ring or patch). With cyclic dosing, regular withdrawal bleeding still occurs, although the amount of blood loss is significantly reduced, and some will still experience menstrual symptoms during the hormone-free interval [41,42].

(See "Combined estrogen-progestin oral contraceptives: Patient selection, counseling, and use", section on 'Administration and use'.)

(See "Contraception: Transdermal contraceptive patches", section on 'Administration'.)

(See "Contraception: Hormonal contraceptive vaginal rings", section on 'Administration and use'.)

For patients who desire oral pills, shortening the hormone-free interval from the traditional seven to fewer days of placebo or use of low-dose estrogen during the traditional hormone-free week provides greater ovarian suppression, which may help reduce both the occurrence of symptoms associated with hormone withdrawal and the risk of pregnancy [43]. Withdrawal spotting/bleeding may occur during pill-free intervals. Several 28-day oral contraceptive formulations, which include a shortened hormone-free interval, are available (these can be referred to as 24/4 oral contraceptive formulations) (table 3).

For the transdermal patch, the volume of withdrawal bleeding is reduced to a level similar to that of the estrogen-progestin pills. Unscheduled bleeding is common in the first months of use but then subsides. Cyclic use of the vaginal ring results in cycle control that is at least as good as that of the estrogen-progestin pills and transdermal patch.

Patients who suffer from menstrual symptoms with cyclic dosing or who have medical indications or preferences for no bleeding may benefit from an extended or continuous dose regimen. (See 'Combined estrogen-progestin methods' above.)

Levonorgestrel intrauterine device (LNG 19.5 mg) — The lower levonorgestrel dose in the levonorgestrel 19.5 mg intrauterine device (LNG 19.5 IUD; commercial name Kyleena) is a highly effective contraceptive that also reduces the volume of withdrawal bleeding. While it can result in amenorrhea in approximately 12 percent of users by one year, this rate is approximately one-half that for the LNG 52 mg IUDs [44]. As the LNG 19.5 mg IUD is approved for up to five years of use, we prefer this device to the LNG 13.5 mg IUD (commercial name Skyla), which also reduces the volume of withdrawal bleeding but is only approved for contraception for up to three years. Discussion of the various IUD devices and impact on bleeding patterns is reviewed in detail elsewhere. (See "Intrauterine contraception: Background and device types".)

OTHER — Medications other than contraceptives and gonadotropin-releasing hormone agonists can be used to suppress menstruation. These are generally used when there is a specific medical indication for the approaches below compared with the more commonly used approaches above. These drugs are costly, often have significant side effects, and may not universally suppress ovulation; therefore, an additional contraceptive method may be necessary (eg, male or female condoms), and ovulation-related symptoms may not subside. Some examples are:

Postmenopausal hormone therapy – A postmenopausal estrogen-progestin formulation can be used off-label to suppress menstruation. This is oral ethinyl estradiol (EE) 5 mcg combined with norethindrone acetate (NETA) 1 mg (available as a 28-day continuous formulation; eg, Jinteli 1/5 and other generics [45]), which is marketed for treatment of menopausal symptoms. Because of its low estrogen dose, some clinicians prescribe this 1/5 menopausal formulation off-label to premenopausal patients desiring menstrual suppression when lower estrogen doses are preferred, such as for females >35 years of age who are obese, have controlled hypertension, smoke cigarettes, or have migraines without aura. While not studied expressly for this purpose, the lower estrogen dose, as compared with that in oral contraceptive pills, is believed to have a reduced risk of thromboembolic events. (See "Menopausal hormone therapy: Benefits and risks".)

Many premenopausal users develop amenorrhea during use of this 1/5 formulation. Because the dose of NETA is lower, this EE/NETA formulation likely causes fewer undesirable progestin-related side effects than NETA 5 mg tablets. Although the 1 mg dose of NETA is sufficient to prevent ovulation (and, in fact, is higher than the dose in some marketed oral contraceptives), this 1/5 formulation is not approved for use as a contraceptive, and consistent back-up contraception (eg, condom use) should be advised if this formulation is prescribed to patients who need birth control. (See "Abnormal uterine bleeding in nonpregnant reproductive-age patients: Management", section on 'Role of noncontraceptive estrogen-progestin formulations'.)

Danazol – Danazol suppresses pituitary output of follicle-stimulating hormone and luteinizing hormone, which leads to atrophy of endometrial tissue. However, androgenic side effects, such as acne, hirsutism, and deepening voice, limit its use. (See "Endometriosis: Treatment of pelvic pain", section on 'Danazol'.)

IMPACT ON FERTILITY — After contraceptive cessation, patients who use hormonal contraceptives continuously or long term do not appear to have reduced fecundity compared with patients using nonhormonal methods. While there may be a brief delay in conception for patients who stop hormonal contraceptives compared with patients discontinuing nonhormonal methods, the reported 12-month conception rates are similar. (See "Combined estrogen-progestin oral contraceptives: Patient selection, counseling, and use", section on 'Return of menses after stopping'.)

The only hormonal contraceptive associated with an extended impact on fertility is depot medroxyprogesterone acetate. (See "Depot medroxyprogesterone acetate (DMPA): Formulations, patient selection and drug administration".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Contraception".)

SUMMARY AND RECOMMENDATIONS

Rationale for menstrual suppression – Suppression of menstruation has medical and personal benefits for many patients and is cost-effective. Menstruation (ovulation followed by withdrawal bleeding) is not physiologically necessary. (See 'Gynecologic' above.)

Reduction of menstrual volume – For patients whose goal is reduction, but not necessarily elimination, of monthly blood flow, we suggest cyclic use of estrogen-progestin contraceptives rather than progestins or continuous use of combined hormonal preparations (Grade 2C). Users of the estrogen-progestin pill, transdermal patch, or vaginal ring should not have any contraindications to use of contraceptive doses of estrogen. (See 'Cyclic estrogen-progestin methods' above.)

Amenorrhea – For patients whose goal is amenorrhea, depot medroxyprogesterone acetate (DMPA), continuous combined estrogen-progestin contraceptives, and levonorgestrel (LNG) 52 mg intrauterine device are all effective.

Although randomized trials comparing these drugs have not been performed, DMPA appears to have the highest rate of amenorrhea, while the LNG 52 mg intrauterine device (IUD) is the most convenient and appears to be associated with higher continuation rates and fewer bothersome side effects than progestin injections. For these reasons, many patients select the IUD. (See 'Depot medroxyprogesterone acetate' above and 'Combined estrogen-progestin methods' above and 'Levonorgestrel intrauterine device (LNG 52 mg)' above.)

For patients who desire amenorrhea, need to avoid estrogen, and prefer a long-acting reversible contraceptive, we suggest the LNG 52 mg IUD or DMPA rather than the progestin-releasing implant (Grade 2C). We prefer the IUD and progestin injections for these patients as rates of amenorrhea are higher compared with the implant. (See 'Levonorgestrel intrauterine device (LNG 52 mg)' above and 'Depot medroxyprogesterone acetate' above.)

  1. Altshuler AL, Hillard PJ. Menstrual suppression for adolescents. Curr Opin Obstet Gynecol 2014; 26:323.
  2. ACOG Clinical Consensus No. 3: General Approaches to Medical Management of Menstrual Suppression. Obstet Gynecol 2022; 140:528.
  3. Lin K, Barnhart K. The clinical rationale for menses-free contraception. J Womens Health (Larchmt) 2007; 16:1171.
  4. den Tonkelaar I, Oddens BJ. Preferred frequency and characteristics of menstrual bleeding in relation to reproductive status, oral contraceptive use, and hormone replacement therapy use. Contraception 1999; 59:357.
  5. Andrist LC, Arias RD, Nucatola D, et al. Women's and providers' attitudes toward menstrual suppression with extended use of oral contraceptives. Contraception 2004; 70:359.
  6. Sulak PJ, Kuehl TJ, Ortiz M, Shull BL. Acceptance of altering the standard 21-day/7-day oral contraceptive regimen to delay menses and reduce hormone withdrawal symptoms. Am J Obstet Gynecol 2002; 186:1142.
  7. Jacobson JC, Likis FE, Murphy PA. Extended and continuous combined contraceptive regimens for menstrual suppression. J Midwifery Womens Health 2012; 57:585.
  8. Edelman A, Micks E, Gallo MF, et al. Continuous or extended cycle vs. cyclic use of combined hormonal contraceptives for contraception. Cochrane Database Syst Rev 2014; :CD004695.
  9. Kaplowitz PB, Oberfield SE. Reexamination of the age limit for defining when puberty is precocious in girls in the United States: implications for evaluation and treatment. Drug and Therapeutics and Executive Committees of the Lawson Wilkins Pediatric Endocrine Society. Pediatrics 1999; 104:936.
  10. American College of Obstetricians and Gynecologists Committee on Adolescent Health Care. ACOG Committee Opinion No. 448: Menstrual manipulation for adolescents with disabilities. Obstet Gynecol 2009; 114:1428.
  11. Schneider MB, Fisher M, Friedman SB, et al. Menstrual and premenstrual issues in female military cadets: a unique population with significant concerns. J Pediatr Adolesc Gynecol 1999; 12:195.
  12. Frankovich RJ, Lebrun CM. Menstrual cycle, contraception, and performance. Clin Sports Med 2000; 19:251.
  13. Jain V, Wotring V. Medically induced amenorrhea in female astronauts. NPJ Microgravity 2016.
  14. Eagan SM. Menstrual Suppression for Military Women: Barriers to Care in the United States. Obstet Gynecol 2019; 134:72.
  15. Braunstein JB, Hausfeld J, Hausfeld J, London A. Economics of reducing menstruation with trimonthly-cycle oral contraceptive therapy: comparison with standard-cycle regimens. Obstet Gynecol 2003; 102:699.
  16. van den Heuvel MW, van Bragt AJ, Alnabawy AK, Kaptein MC. Comparison of ethinylestradiol pharmacokinetics in three hormonal contraceptive formulations: the vaginal ring, the transdermal patch and an oral contraceptive. Contraception 2005; 72:168.
  17. Devineni D, Skee D, Vaccaro N, et al. Pharmacokinetics and pharmacodynamics of a transdermal contraceptive patch and an oral contraceptive. J Clin Pharmacol 2007; 47:497.
  18. Nelson AL, Kaunitz AM, Kroll R, et al. Efficacy, safety, and tolerability of a levonorgestrel/ethinyl estradiol transdermal delivery system: Phase 3 clinical trial results. Contraception 2021; 103:137.
  19. Anderson FD, Hait H. A multicenter, randomized study of an extended cycle oral contraceptive. Contraception 2003; 68:89.
  20. Anderson FD, Gibbons W, Portman D. Long-term safety of an extended-cycle oral contraceptive (Seasonale): a 2-year multicenter open-label extension trial. Am J Obstet Gynecol 2006; 195:92.
  21. Sulak PJ, Kuehl TJ, Coffee A, Willis S. Prospective analysis of occurrence and management of breakthrough bleeding during an extended oral contraceptive regimen. Am J Obstet Gynecol 2006; 195:935.
  22. Machado RB, de Melo NR, Maia H Jr. Bleeding patterns and menstrual-related symptoms with the continuous use of a contraceptive combination of ethinylestradiol and drospirenone: a randomized study. Contraception 2010; 81:215.
  23. Miller L, Verhoeven CH, Hout Ji. Extended regimens of the contraceptive vaginal ring: a randomized trial. Obstet Gynecol 2005; 106:473.
  24. Guazzelli CA, Barreiros FA, Barbosa R, et al. Extended regimens of the vaginal contraceptive ring: cycle control. Contraception 2009; 80:430.
  25. Barreiros FA, Guazzelli CA, Barbosa R, et al. Extended regimens of the contraceptive vaginal ring: evaluation of clinical aspects. Contraception 2010; 81:223.
  26. Depo-provera- medroxyprogesterone acetate injection, suspension. US Food and Drug Administration (FDA) approved product information. Revised February 2019. US National Library of Medicine. www.dailymed.nlm.nih.gov (Accessed on June 13, 2019).
  27. Diedrich JT, Zhao Q, Madden T, et al. Three-year continuation of reversible contraception. Am J Obstet Gynecol 2015; 213:662.e1.
  28. Mirena package insert. http://labeling.bayerhealthcare.com/html/products/pi/Mirena_PI.pdf (Accessed on June 12, 2017).
  29. Liletta package insert. http://pi.actavis.com/data_stream.asp?product_group=1960&p=pi&language=E (Accessed on April 24, 2015).
  30. Skyla package insert. http://labeling.bayerhealthcare.com/html/products/pi/Skyla_PI.pdf (Accessed on April 24, 2015).
  31. Hidalgo M, Bahamondes L, Perrotti M, et al. Bleeding patterns and clinical performance of the levonorgestrel-releasing intrauterine system (Mirena) up to two years. Contraception 2002; 65:129.
  32. Lukes AS, Reardon B, Arepally G. Use of the levonorgestrel-releasing intrauterine system in women with hemostatic disorders. Fertil Steril 2008; 90:673.
  33. Kadir RA, Chi C. Levonorgestrel intrauterine system: bleeding disorders and anticoagulant therapy. Contraception 2007; 75:S123.
  34. Chi C, Huq FY, Kadir RA. Levonorgestrel-releasing intrauterine system for the management of heavy menstrual bleeding in women with inherited bleeding disorders: long-term follow-up. Contraception 2011; 83:242.
  35. Irvine GA, Campbell-Brown MB, Lumsden MA, et al. Randomised comparative trial of the levonorgestrel intrauterine system and norethisterone for treatment of idiopathic menorrhagia. Br J Obstet Gynaecol 1998; 105:592.
  36. Vercellini P, Bracco B, Mosconi P, et al. Norethindrone acetate or dienogest for the treatment of symptomatic endometriosis: a before and after study. Fertil Steril 2016; 105:734.
  37. Nexplanon- etonogestrel implant. US Food and Drug Administration (FDA) approved product information. Revised October, 2018. US National Library of Medicine. www.dailymed.nlm.nih.gov (Accessed on June 13, 2019).
  38. McNicholas C, Swor E, Wan L, Peipert JF. Prolonged use of the etonogestrel implant and levonorgestrel intrauterine device: 2 years beyond Food and Drug Administration-approved duration. Am J Obstet Gynecol 2017.
  39. Ali M, Akin A, Bahamondes L, et al. Extended use up to 5 years of the etonogestrel-releasing subdermal contraceptive implant: comparison to levonorgestrel-releasing subdermal implant. Hum Reprod 2016; 31:2491.
  40. Taylor HS, Giudice LC, Lessey BA, et al. Treatment of Endometriosis-Associated Pain with Elagolix, an Oral GnRH Antagonist. N Engl J Med 2017; 377:28.
  41. Sulak PJ, Scow RD, Preece C, et al. Hormone withdrawal symptoms in oral contraceptive users. Obstet Gynecol 2000; 95:261.
  42. Sulak PJ, Cressman BE, Waldrop E, et al. Extending the duration of active oral contraceptive pills to manage hormone withdrawal symptoms. Obstet Gynecol 1997; 89:179.
  43. Fels H, Steward R, Melamed A, et al. Comparison of serum and cervical mucus hormone levels during hormone-free interval of 24/4 vs. 21/7 combined oral contraceptives. Contraception 2013; 87:732.
  44. Kyleena- levonorgestrel intrauterine device.. US Food and Drug Administration (FDA) approved product information. Revised March, 2018.. US National Library of Medicine. www.dailymed.nlm.nih.gov (Accessed on June 26, 2019).
  45. Symons J, Kempfert N, Speroff L. Vaginal bleeding in postmenopausal women taking low-dose norethindrone acetate and ethinyl estradiol combinations. The FemHRT Study Investigators. Obstet Gynecol 2000; 96:366.
Topic 5423 Version 36.0

References

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